The overall objective of this research proposal is to evaluate the hypothesis that mammalian ovulation occurs as the result of an inflammatory reaction in mature ovarian follicles. The initial phase of the research plan consists of a comprehensive analysis of the capacity of a variety of anti-inflammatory agents to inhibit ovulation. The various anti-inflammatory agents will be given by oral and intravenous routes to rabbits, and the ovaries will be examined 20-24 hours later for evidence of ovulation. These initial experiments will be useful not only in the evaluation of the working hypothesis-they will also examine the potential value of anti-inflammatory agents as regulators of mammalian fertility. The second phase of the project will determine the effect of different types of anti-inflammatory agents on follicular production of prostaglandins, which are well-known mediators of inflammation. Prostaglandin levels will be determined by radioimmunoassay. The third phase of the project will analyse ovulatory tissue for the production of several other common mediators and by-products of inflammatory reactions. Histamine, bradykinin, Hageman factor, and component five (C5) will be determined by isotope-enzyme microassay, radioimmunoassay, a prekallikrein activation assay, and by radial immunodiffusion, respectively. If this study should reveal that several metabolites of inflammatory reactions are synthesized and/or released during the ovulatory process, and that a wide variety of anti-inflammatory agents can inhibit ovulation, then the project will have presented substantial evidence to support the hypothesis that the mechanism of mammalian ovulation involves an inflammatory reaction.